18-week, randomized, double-blind, placebo controlled, forced titration study of patients with type 2 diabetes

Conditions: Type 2 Diabetes Mellitus

Summary: designed to evaluate dose response of force-titrated prandial administration of ti as compared to placebo (tp) in subjects with type 2 diabetes who were suboptimally controlled


Eligibility criteria:
inclusion criteria: * male and females patients from 18 to \<80 years of age * clinical diagnosis of type 2 diabetes mellitus * duration of diabetes of \>3 years and \<20 years * glycemic control at upper end of acceptable level or sub-optimal in control (hba1c between 7.0% and 12?0%) * confirmation of diagnosis of diabetes such as a history of 2 hour postprandial blood glucose \>11.1 mmol/l (200 mg/dl) or following a glucose tolerance test * a minimum of 2 months of treatment with a stable dose of one or more of the following anti-hyperglycemic agents: sulphonylureas, alpha glucosidase inhibitors, metformin, meglitinides, thiazolidinediones and/or lantus basal insulin therapy * fbg:\>6 mmol/l (108 mg/dl) * c-peptide: \>0.5 nmol/l * bmi \<38 kg/m2 * baseline dlco, fvc, fev1 \>75% of predicted normal * subjects who, in the opinion of the investigator, will be able to complete this study * written informed consent exclusion criteria: * severe complications of diabetes including history of: blindness from or grade iii or iv diabetic retinopathy, renal failure requiring dialysis or transplantation, amputation of limbs or digits related to diabetic vasculopathy or foot ulcers * treatment with another investigational drug within 3 months prior to study entry and for the duration of the study * history of drug or alcohol dependency * significant hepatic disease (as evidenced by alt or ast \>3 times the normal upper reference range or bilirubin \>1.5 times the normal upper reference range) * significant renal disease (as evidenced by creatinine \>1.5 mg/dl for males or \>1.3 mg/dl for females) or proteinuria \>1,000 mg/24 hours * history of chronic obstructive pulmonary disease, or history of other known chronic pulmonary diseases, such as reactive airway disease, chronic bronchitis, emphysema, or asthma * heart disease graded as class iii or class iv according to new york heart association criteria * prior treatment with , or participation in a clinical study involving an inhaled insulin product * smokers * current use of preprandial or prandially administered fast-acting or rapid acting insulin or insulin analogs * previous participation in a ti or tp clinical trial * allergy to insulin or to any drugs to be used as part of the clinical trial * history of malignancy within 5 years of study entry (other than basal cell carcinoma) * anemia (hemoglobin level less than 11 g/dl for females or 12 g/dl for males at study entry) * diagnosis of acquired immunodeficiency syndrome (aids) and aids related complex a major psychiatric disorder that will preclude satisfactory participation in this study * subjects who have had a myocardial infarction or stroke within the preceding 6 months * prior diagnosis of systemic autoimmune or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine * history of severe or multiple allergies * progressive fatal disease * recent loss (within the past 2 months) of \>5% of body weight * evidence of "moderate" or greater ketones in urine or history of ketoacidosis * use of medications known to modify glucose metabolism or the ability to recover from hypoglycemia such as oral, parenteral and inhaled steroids, or greater than 25 mg hydrochlorothiazide daily * women who are pregnant or lactating * women of childbearing potential practicing inadequate birth control (adequate birth control is defined as using oral contraceptives, condoms or diaphragms with spermicide, intrauterine devices, or surgical sterilization).